NM_000597.3:c.442+9238A>T

Variant names:

• chr2-216643203-A-T
• rs9341134
• NM_000597.3:c.442+9238A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000597.3(IGFBP2):​c.442+9238A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0882 in 152,122 control chromosomes in the GnomAD database, including 709 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.088 (709 hom., cov: 32)
• Consequence: IGFBP2 NM_000597.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.485
• Publications: 4 publications found

Genes affected

IGFBP2 (HGNC:5471): (insulin like growth factor binding protein 2) The protein encoded by this gene is one of six similar proteins that bind insulin-like growth factors I and II (IGF-I and IGF-II). The encoded protein can be secreted into the bloodstream, where it binds IGF-I and IGF-II with high affinity, or it can remain intracellular, interacting with many different ligands. High expression levels of this protein promote the growth of several types of tumors and may be predictive of the chances of recovery of the patient. Several transcript variants, one encoding a secreted isoform and the others encoding nonsecreted isoforms, have been found for this gene. [provided by RefSeq, Sep 2015]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGFBP2	NM_000597.3	c.442+9238A>T		intron_variant	Intron 1 of 3	ENST00000233809.9	NP_000588.3
IGFBP2	NM_001313992.2	c.-57+9928A>T		intron_variant	Intron 1 of 3		NP_001300921.1
IGFBP2	NM_001313993.2	c.-57+10189A>T		intron_variant	Intron 1 of 3		NP_001300922.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGFBP2	ENST00000233809.9	c.442+9238A>T		intron_variant	Intron 1 of 3	1	NM_000597.3	ENSP00000233809.4
IGFBP2	ENST00000434997.1	c.-57+10189A>T		intron_variant	Intron 1 of 2	3		ENSP00000401698.1
IGFBP2	ENST00000490362.1	n.537+9238A>T		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.0882 AC: 13401 AN: 152004 Hom.: 707 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0696

Gnomad ASJ AF: 0.0791

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.0245

Gnomad FIN AF: 0.0605

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0742

Gnomad OTH AF: 0.0828

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0882 AC: 13414 AN: 152122 Hom.: 709 Cov.: 32 AF XY: 0.0860 AC XY: 6399 AN XY: 74374

African (AFR) AF: 0.146 AC: 6049 AN: 41482

American (AMR) AF: 0.0695 AC: 1062 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0791 AC: 274 AN: 3466

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5172

South Asian (SAS) AF: 0.0241 AC: 116 AN: 4812

European-Finnish (FIN) AF: 0.0605 AC: 641 AN: 10594

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0742 AC: 5043 AN: 67994

Other (OTH) AF: 0.0819 AC: 173 AN: 2112

Alfa AF: 0.0295 Hom.: 24

Bravo AF: 0.0921

Asia WGS AF: 0.0270 AC: 94 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	4.4
DANN	Benign	0.73
PhyloP100		0.48
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9341134; hg19: chr2-217507926;